Abstract
Purpose :
Despite some recent progress with retinal prosthetics the optimal duration for the electric stimulus remains unknown. Recently, we reported that an identical electric pulse elicits distinct responses in ON and OFF types of retinal ganglion cells (RGCs). The temporal properties to repetitive stimuli were also different in the two types. Thus, we hypothesize that varying the duration of the stimulus would alter the responses in different ways across different types of RGCs, thus raising a possibility to selectively activate one type over the other. Here, we systematically investigated network-mediated responses in various types of RGCs as a function of stimulus duration.
Methods :
Cell-attached patch clamp was used to record spikes from RGCs in the rabbit retina explant. RGCs were classified as ON or OFF cells by their response to stationary flashes and further classified as Brisk Transient (BT) or Brisk Sustained (BS) subtypes by their electric responses. After cell type classification, monophasic half-sinusoidal stimuli with durations of 5-100ms and amplitudes adjusted to keep total charge constant were presented to targeted RGCs. Each stimulus was repeated 7 times. We recorded the spiking activity in 7 ON BT, 10 ON BS, 8 OFF BT, and 14 OFF BS cells.
Results :
The pattern of network-mediated responses was unique for each type of RGC across a wide range of stimulus durations. We found that: 1) In ON cells, there was a distinct difference between BT and BS subtypes in number of spikes elicited by same stimulus duration but the distinction was less clear across OFF subtypes. 2) Across the durations tested, both types of ON cells showed dramatic changes in the number of evoked spikes while OFF cells showed smaller changes in their responses. 3) This disparity between ON and OFF cells resulted in the ratio of spikes elicited by the two types to be maximized at a stimulus duration of ~10 ms.
Conclusions :
ON and OFF types of RGCs exhibited fundamental differences in responses to a wide range of durations of the electric stimulus, resulting in variable levels of ON vs. OFF selectivity at different durations. Together with our previous report that an electric stimulus evokes more physiological responses from ON cells than OFF cells, the finding here of a stimulus duration that maximizes the ON/OFF response ratio may offer enhanced clinical guidelines to retinal prosthetic community.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.